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Song Zhang, Xin Wang, Hao Gu, Jun-Qi Liu Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Jun-Qi Liu, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jian-She East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 13938550770, Email fccliujq@zzu.edu.cnObjective: This study was to investigate the feasibility and safety of anlotinib monotherapy for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) retrospectively.Methods: This study was designed as a real-world study. A total of 83 patients with advanced or metastatic ESCC who received anlotinib monotherapy were included. Demographic characteristics of the patients, efficacy data of the treatment and adverse reactions during the treatment were documented and analyzed through the electronic medical record system in the hospital. All the patients were followed up regularly. The primary endpoint of this study was progression-free survival (PFS), secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety profile and PFS analysis according to adverse reactions.Results: A total of 83 patients with ESCC who received anlotinib monotherapy were included. Partial response was observed in 7 patients, stable disease was noted in 51 patients and progressive disease was found in 25 patients, which yielded an ORR of 8.4% (95% CI: 3.5– 16.6%), and a DCR of 69.9% (95% CI: 58.8– 79.5%). Furthermore, the median PFS of the 83 patients with advanced ESCC was 3.3 months (95% CI: 2.20– 4.40) and the median OS was 7.8 months (95% CI: 5.40– 10.20). Common adverse reactions among the 83 patients were hypertension (51.8%), fatigue (48.2%), weight loss (41.0%), diarrhea (34.9) and hand-foot syndrome (30.1%). Correlation analysis between hypertension status and PFS suggested that PFS of the patients with hypertension was longer than that of those with non-hypertension (median PFS: 4.5 vs 3.0 months, P = 0.019).Conclusion: Anlotinib monotherapy demonstrated promising efficacy and tolerable toxicity for patients with previously treated advanced or metastatic ESCC. Hypertension that occurs during anlotinib administration might be used as a potential biomarker to predict PFS of patients with ESCC. The conclusion should be confirmed in prospective clinical trials subsequently.Keywords: esophageal squamous cell carcinoma, anlotinib, efficacy, safety, hypertension, biomarker

Zheng Liu,1,* Fang Shi,1 Jun-Xia Liu,1 Jia-Qi Liu,2 Jing Li,1 Qian Wang,1 Hui Wang,1 Chang-Lan Gao,3 Jian-Min Li,1 Dong-Fang Zhao1,* 1Department of Respiratory Medicine, The Petroleum Clinical Medical College of Hebei Medical University, Langfang, Hebei, 065000, People’s Republic of China; 2Schulich School of Medical and Dentistry-Honour Specialization in Interdisciplinary Medical Science and Major in Pharmacology, Western University, London, Ontario, Canada; 3Department of Critical Care Medicine, Langfang Fourth Hospital, Langfang, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zheng Liu; Dong-Fang ZhaoDepartment of Respiratory Medicine, The Petroleum Clinical Medical College of Hebei Medical University, Langfang, Hebei, 065000, People’s Republic of ChinaTel +86 316 2077814; +86 316 2077345Email zhengl06drsun@163.com; dongfang06_walker@21cn.comBackground: The World Health Organization (WHO) strongly suggests using corticosteroids in patients with severe coronavirus disease 2019 (COVID-19). Similarly, a large randomized controlled clinical trial (RCT) in the UK found that dexamethasone effectively reduced the mortality rate in severe COVID-19 patients. However, the safety profile of corticosteroids has been a controversial area of study.Case Description: A case of a COVID-19 patient is described and the clinical characteristics are observed as the mildly symptomatic patient progresses into a critically ill patient and during their dramatic improvement with corticosteroid therapy in the early stage of the deterioration process with COVID-19 pneumonia.Conclusion: The most suitable timing and dosage for the use of corticosteroids to maximize its effect during the worsening of COVID-19 pneumonia are discussed. One of the main pathophysiological hypotheses for severe COVID-19 patients is related to cytokine storm and virus load, which can be effectively treated with corticosteroid therapy.Keywords: COVID-19 pneumonia, cytokine storm, corticosteroids, clinical characteristics

Wen-Ling Wang,1,2 Shuang Liang,1 Fang-Lei Zhu,1 Jie-Qiong Liu,1 Si-Yang Wang,1 Xiang-Mei Chen,1 Guang-Yan Cai1 On behalf of the C-OPTION study group1Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, People’s Republic of China; 2General Internal Medicine Department, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaPurpose: The prevalence of depression and the relationship between depression and kidney function and health-related quality of life (HRQOL) are not well understood in elderly patients with predialysis chronic kidney disease (CKD). This study aimed to evaluate the prevalence of depression and the association between depression and kidney function and HRQOL.Patients and methods: In this cross-sectional study, 1079 elderly participants with CKD were recruited at 32 clinical centers located within 26 cities throughout 24 provinces in China. Demographic information and laboratory analyses were collected. Symptoms of depression were assessed using the 15-item Geriatric Depression Scale (GDS-15). HRQOL was evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36) instrument.Results: The prevalence of depression was 23.0%. The estimated glomerular filtration rate (eGFR) was negatively correlated with the GDS score whether it was treated as a categorical variable (r=−0.097, P=0.001) or as a continuous variable (r=−0.100, P=0.001). Marital status, education level, history of CVD and diabetes, CKD stage and proteinuria confirmed to be independent and significant predictors of depression in patients with CKD. Compared with CKD 1–2 patients, we observed an increase of 0.541 and 4.171 in the odds for developing depression in patients CKD 4 (odds ratio [OR] =1.541; P=0.031) and CKD 5 (odds ratio [OR] =5.171; P

Jie-qiong Liu,1,2 Guang-yan Cai,1 Si-yang Wang,1 Yu-huan Song,1 Yuan-yuan Xia,1 Shuang Liang,1 Wen-ling Wang,1 Sa-sa Nie,1 Zhe Feng,1 Xiang-mei Chen1 1Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Disease, Beijing, China; 2Department of Nephrology, Chinese PLA 401 Hospital, Qingdao, China Objectives: The most serious adverse reaction of cisplatin is acute kidney injury (AKI). Cisplatin-induced acute kidney injury (CIA) has no specific preventive measures. This study aims to explore the characteristics and risk factors for CIA in the elderly and to identify potential methods to reduce CIA. Materials and methods: Patients ≥18 years old, with primary tumors, who received initial cisplatin chemotherapy and whose serum creatinine (SCr) values were measured within 2 weeks pre- and postcisplatin treatment and who had complete medical records, were selected from a single center from January 1, 2013 to December 31, 2015. The exclusion criteria included radiotherapy or surgery, recurrent tumors, previous cisplatin treatment, lack of any SCr values before or after cisplatin therapy, and incomplete medical records. Results: Out of a total of 527 patients, 349 were elderly. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use (9.2%) was more prevalent in the elderly than in younger patients (2.8%, p = 0.007). The dosage of cisplatin treatment was lower in the elderly, but the incidence of CIA (9.46%) was higher in the elderly than in younger patients (3.37%). There were significant differences in the SCr levels, estimated glomerular filtration rate, ACEI/ARB use, and whether a single application of cisplatin was administered, between the elderly AKI group and the non-AKI group. Multivariable analysis showed that administration of a single application of cisplatin (OR 2.853, 95% CI: 1.229, 6.621, p = 0.015) and ACEI/ARB use (OR 3.398, 95% CI: 1.352, 8.545, p = 0.009) were predictive factors for developing CIA in the elderly. Conclusion: The incidence of CIA in the elderly was higher than in younger patients. ACEI/ARB usage and administration of a single application of cisplatin were independent risk factors for CIA in the elderly. Keywords: cisplatin-induced acute kidney injury, elderly, clinical characteristics, risk factors

Lixia Mao,1,* Jiaqiang Liu,1,* Jinglei Zhao,1 Jiang Chang,2 Lunguo Xia,1 Lingyong Jiang,1 Xiuhui Wang,2 Kaili Lin,2,3 Bing Fang11Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Top Priority Clinical Medical Center of Shanghai Municipal Commission of Health and Family Planning, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Jiao Tong University, 2State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 3Shanghai Engineering Research Center of Tooth Restoration and Regeneration, School of Stomatology, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: The surface structure of bioceramic scaffolds is crucial for its bioactivity and osteoinductive ability, and in recent years, human periodontal ligament stem cells have been certified to possess high osteogenic and cementogenic differential ability. In the present study, hydroxyapatite (HA) bioceramics with micro-nano-hybrid surface (mnHA [the hybrid of nanorods and microrods]) were fabricated via hydrothermal reaction of the α-tricalcium phosphate granules as precursors in aqueous solution, and the effects of mnHA on the attachment, proliferation, osteogenic and cementogenic differentiations of human periodontal ligament stem cells as well as the related mechanisms were systematically investigated. The results showed that mnHA bioceramics could promote cell adhesion, proliferation, alkaline phosphatase (ALP) activity, and expression of osteogenic/cementogenic-related markers including runt-related transcription factor 2 (Runx2), ALP, osteocalcin (OCN), cementum attachment protein (CAP), and cementum protein (CEMP) as compared to the HA bioceramics with flat and dense surface. Moreover, mnHA bioceramics stimulated gene expression of low-density lipoprotein receptor-related protein 5 (LRP5) and β-catenin, which are the key genes of canonical Wnt signaling. Moreover, the stimulatory effect on ALP activity and osteogenic and cementogenic gene expression, including that of ALP, OCN, CAP, CEMP, and Runx2 of mnHA bioceramics could be repressed by canonical Wnt signaling inhibitor dickkopf1 (Dkk1). The results suggested that the HA bioceramics with mnHA could act as promising grafts for periodontal tissue regeneration.Keywords: surface topography, periodontal ligament stem cells, Wnt signaling pathway, bioceramics, periodontal reconstruction

AbstractThere is intense and growing interest in one-dimensional (1-D) nanostructures from the perspective of their synthesis and unique properties, especially with respect to their excellent optical response and an ability to form heterostructures. This review discusses alternative approaches to preparation and organization of such structures, and their potential properties. In particular, molecular-scale printing is highlighted as a method for creating organized pre-cursor structure for locating nanowires, as well as vapor–liquid–solid (VLS) templated growth using nano-channel alumina (NCA), and deposition of 1-D structures with glancing angle deposition (GLAD). As regards novel optical properties, we discuss as an example, finite size photonic crystal cavity structures formed from such nanostructure arrays possessing highQand small mode volume, and being ideal for developing future nanolasers.

Chronic hypoxia (CH) is a common cause of pulmonary hypertension (PH). Accumulating evidence suggests that changes in the activity of endothelin (ET)-1 receptors may play an important role in CH-induced PH. After 3 weeks of CH (10% O2) exposure, we found that the isolated intra-pulmonary artery (PA) constrictor response to ET-1 was significantly increased in wild-type (wt) mice. The administration of Cu/Zn superoxide dismutase (SOD) markedly reduced the CH-enhanced maximal PA constrictor response to ET-1, demonstrating the contribution of superoxide to CH-enhanced PA constrictor responses. Using mice that are completely deficient in gp91phox (a subunit protein of the superoxide producing nicotinamide adenine dinucleotide phosphate [NADPH] oxidase), we found that CH-enhanced PA constriction to ET-1 was completely blocked (decreases in mean [+/- SE] maximal isometric tension from 5.43 +/- 0.35 to 3.33 +/- 0.19 mN; n = 7; p < 0.01). Using a lucigenin-enhanced chemiluminescence technique to measure superoxide, we found that the 3 weeks of CH significantly increased superoxide levels in PA isolated from wt mice. The addition of ET-1 further increased superoxide production. To demonstrate that the increased chemiluminescence is due to superoxide generation, we added Cu/Zn SOD, which markedly decreased chemiluminescence, demonstrating the specificity of this assay. When gp91phox knockout mice were exposed to CH, they had significantly reduced levels of superoxide compared to CH-treated wt mice. Our results demonstrate that the CH-enhanced PA constrictor response to ET-1 is mediated by NADPH oxidase (gp91phox)-derived superoxide overproduction that may contribute to the pathogenesis of CH-induced PH. [ABSTRACT FROM AUTHOR]

Background and Purpose: To investigate the impact of radiotherapy (RT) on the risk of secondary pelvic neoplasms (SPN) and the survival outcomes of patients following a diagnosis of female patients with genital neoplasm(FGN)., Materials and Methods: Utilizing SEER databases, this study involved 102,895 patients from nine oncology centers, spanning 1990 to 2015. We employed the Fine-Gray competing risks regression methodology to chart the trajectory of SPN development and used the Kaplan-Meier method to calculate the 10-year overall survival rates., Results: This study included 25,774 patients in the RT group and 77,121 in the non-radiotherapy (NRT) group. The cumulative incidence rate of SPN was 5.10 % in the RT group and 3.42 % in the NRT group. The RT group showed a significantly higher incidence of bladder cancer (adjusted hazard ratio [HR]: 1.75; 95 % confidence interval [CI]: 1.43-2.14; P < 0.05), colon cancer (adjusted HR: 1.32; 95 % CI: 1.16-1.49; P < 0.05), and rectal cancer (adjusted HR: 1.34; 95 % CI: 1.10-1.65; P < 0.05) compared to the NRT group. After propensity score matching, patients in the RT group who developed bladder cancer had significantly reduced 10-year survival rates compared to patients with primary pelvic tumors (P = 0.01)., Conclusion: RT is identified as an independent risk factor for the development of SPN in patients with FGN. Patients with FGN who undergo RT demonstrate a significant increase in the risk of developing secondary neoplasms, specifically bladder cancers, and experience a reduction in 10-year survival rates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era., Methods: Data on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed., Results: The 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome., Conclusion: NPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local-regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Dry eye disease (DED) is highly prevalent worldwide, leading to increased medical costs, economic burdens on families and society, and a diminished quality of life for patients. The utilization of autologous serum eye drops (ASEDs) for the treatment of DED is progressively rising., Objective: To further evaluate the efficacy and safety of ASEDs in the treatment of DED., Methods: A thorough search for randomized controlled trials (RCTs) was conducted across eight databases, including PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. This search encompassed the inception of each database up to April 1, 2024, with a specific focus on identifying RCTs evaluating the efficacy and safety of ASEDs for the treatment of DED. Data analysis was conducted utilizing Stata 15.0 software and the Cochrane Risk of Bias Assessment Tool was utilized to appraise the literature's quality., Results: The study encompassed 12 RCTs. In comparison to the use of artificial tears (AT), patients diagnosed with DED who utilized ASEDs displayed elevated the Schirmer test (ST) scores [WMD = 2.35, 95% CI (1.45, 3.24), p < 0.001] and tear-film breakup time (TBUT) scores [WMD = 2.83, 95% CI (2.27, 3.39), p < 0.001], decreased Corneal fluorescence staining (CFS) scores [SMD = -2.11, 95% CI (-3.07, -1.15), p < 0.001] and the Ocular Surface Disease Index (OSDI) scores [WMD = -10.54, 95% CI (-13.31, -7.77), p < 0.001], and experienced a reduced frequency of adverse events [RR = 0.36, 95% CI (0.13, 0.99), p = 0.048]., Conclusion: In this study, ASEDs had been shown to enhance tear secretion, extend tear film break-up time, mitigate corneal epithelial damage, ameliorate OSDI scores, and exhibit greater safety compared to AT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Zeng, Liu, Qiu and He.)

Background: At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China., Methods: A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management., Results: Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at < 34 weeks of gestation (90·0% inborn vs. 50·0% outborn, p < 0·001). The median fraction of inspired oxygen (FiO 2 ) for initial resuscitation was 0·30 for babies born at ≤ 32 weeks of gestation and 0·25 for those born at > 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p < 0·001). Surfactant was used in 51·6% of the DRs. Less invasive surfactant administration (LISA) was used in 49·7% of the hospitals (tertiary hospitals: 55·3% vs. secondary hospitals: 31·5%, p < 0·001). Primary non-invasive ventilation was initiated in approximately 80·0% of the patients. High-frequency oscillation ventilation was primarily reserved for rescue after conventional mechanical ventilation (MV) failure. Caffeine was routinely used during MV in 59·1% of the hospitals. Bedside lung ultrasonography was performed in 54·3% of the health facilities (tertiary hospitals: 61·6% vs. secondary hospitals: 30·4%, p < 0·001). Qualified breast milk banks and Family Integrated Care (FICare) were present in 30·2% and 63·7% of the hospitals, respectively., Conclusions: Significant disparities in resource availability and guidelines adherence were evident across hospitals. Future strategies should address DR facilities and medication access, technical training, staff allocation, and ancillary facility development for a better management of RDS patients in China., (© 2024. The Author(s).)

Plant-associated streptomycetes play important roles in plant growth and development. However, knowledge of volatile-mediated crosstalk between Streptomyces spp. and plants remains limited. In this study, we investigated the impact of volatiles from nine endophytic Streptomyces strains on the growth and development of plants. One versatile strain, Streptomyces setonii WY228, was found to significantly promote the growth of Arabidopsis thaliana and tomato seedlings, confer salt tolerance, and induce early flowering and increased fruit yield following volatile treatment. Analysis of plant growth-promoting traits revealed that S. setonii WY228 could produce indole-3-acetic acid, siderophores, ACC deaminase, fix nitrogen, and solubilize inorganic phosphate. These capabilities were further confirmed through genome sequencing and analysis. Volatilome analysis indicated that the volatile organic compounds emitted from ISP-2 medium predominantly comprised sesquiterpenes and 2-ethyl-5-methylpyrazine. Further investigations showed that 2-ethyl-5-methylpyrazine and sesquiterpenoid volatiles were the primary regulators promoting growth, as confirmed by experiments using the terpene synthesis inhibitor phosphomycin, pure compounds, and comparisons of volatile components. Transcriptome analysis, combined with mutant and inhibitor studies, demonstrated that WY228 volatiles promoted root growth by activating Arabidopsis auxin signaling and polar transport, and enhanced root hair development through ethylene signaling activation. Additionally, it was confirmed that volatiles can stimulate plant abscisic acid signaling and activate the MYB75 transcription factor, thereby promoting anthocyanin synthesis and enhancing plant salt stress tolerance. Our findings suggest that aerial signaling-mediated plant growth promotion and abiotic stress tolerance represent potentially overlooked mechanisms of Streptomyces-plant interactions. This study also provides an exciting strategy for the regulation of plant growth and the improvement of horticultural crop yields within sustainable agricultural practices., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Dual channel photo-driven H 2 O 2 production in pure water on small-scale on-site setups is a promising strategy to provide low-concentrated H 2 O 2 whenever needed. This process suffers, however, strongly from the fast recombination of photo-generated charge carriers and the sluggish oxidation process. Here, insoluble Keggin-type cesium phosphomolybdate Cs 3 PMo 12 O 40 (abbreviated to Cs 3 PMo 12 ) is introduced to carbonized cellulose (CC) to construct S-scheme heterojunction Cs 3 PMo 12 /CC. Dual channel H 2 O 2 photosynthesis from both H 2 O oxidation and O 2 reduction in pure water has been thus achieved with the production rate of 20.1 mmol L -1  g cat. -1  h -1 , apparent quantum yield (AQY) of 2.1% and solar-to-chemical conversion (SCC) efficiency of 0.050%. H 2 O 2 accumulative concentration reaches 4.9 mmol L -1 . This high photocatalytic activity is guaranteed by unique features of Cs 3 PMo 12 /CC, namely, S-scheme heterojunction, electron reservoir, and proton reservoir. The former two enhance the separation of photo-generated charge carriers, while the latter speeds up the torpid oxidation process. In situ experiments reveal that H 2 O 2 is formed via successive single-electron transfer in both channels. In real practice, exposing the reaction system under natural sunlight outdoors successfully results in 0.24 mmol L -1 H 2 O 2 . This work provides a key practical strategy for designing photocatalysts in modulating redox half-reactions in photosynthesis., (© 2024 Wiley‐VCH GmbH.)

Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)-IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV-IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10-null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV-IL-27. Our study revealed a major role for IL-10 in AAV-IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy., (Copyright © 2024 by The American Association of Immunologists, Inc.)

The main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1β, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.

Seven previously undescribed compounds, including one amino acid hybrid sesquiterpene areolatol A (1), two unusual natural sesquiterpenoid skeleton areolatones A-B (2-3) and four benzo[j]fluoranthene areolaranes A-D (4-7) were characterized from Annulohypoxylon areolatum. The structures of the compounds were determined by extensive spectroscopic analysis, X-ray diffraction analysis, and ECD and NMR computational. Notably, areolatol A (1) was the first reported sesquiterpene featuring a 5/7/3-ring system and hybridized with two molecular amino acids. In addition, areolaranes A-D (4-7) were identified as possible chemophenetic markers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2- a ]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H 2 O 2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

Objectives: To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)., Methods: A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022., Results: Among the AAV children, there were 5 males and 20 females, with a median age of onset of 11.0 years. Involvement of the urinary system was seen in 18 cases (72%); respiratory system involvement in 10 cases (40%); skin involvement in 6 cases (24%); eye, ear, and nose involvement in 5 cases (20%); joint involvement in 4 cases (16%); digestive system involvement in 2 cases (8%). Eleven cases underwent kidney biopsy, with 5 cases (46%) showing focal type, 2 cases (18%) showing crescentic type, 2 cases (18%) showing mixed type, and 2 cases (18%) showing sclerotic type. Immune complex deposits were present in 5 cases (45%). Seven cases reached chronic kidney disease (CKD) stage V, with 2 cases resulting in death. Two cases underwent kidney transplantation. At the end of the follow-up period, 2 cases were at CKD stage II, and 1 case was at CKD stage III. Of the 16 cases of microscopic polyangiitis (MPA) group, 13 (81%) involved the urinary system. Of the 9 cases of granulomatosis with polyangiitis (GPA), 6 cases (66%) had sinusitis. Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group ( P <0.05), while red blood cell count and glomerular filtration rate were lower in the MPA group ( P <0.05)., Conclusions: AAV is more common in school-age female children, with MPA being the most common clinical subtype. The onset of AAV in children is mainly characterized by renal involvement, followed by respiratory system involvement. The renal pathology often presents as focal type with possible immune complex deposits. Children with MPA often have renal involvement, while those with GPA commonly have sinusitis. The prognosis of children with AAV is poor, often accompanied by renal insufficiency.

Diabetes mellitus (DM) and obesity have become public issues of global concern. Bariatric surgery for the treatment of obesity combined with type 2 DM has been shown to be a safe and effective approach; however, there are limited studies that have systematically addressed the challenges of surgical treatment of obesity combined with DM. In this review, we summarize and answer the most pressing questions in the field of surgical treatment of obesity-associated DM. I believe that our insights will be of great help to clinicians in their daily practice., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ethnopharmacological Relevance: Arbutin is a naturally occurring glucoside extracted from plants, known for its antioxidant and tyrosinase inhibiting properties. It is widely used in cosmetic and pharmaceutical industries. With in-depth study of arbutin, its application in disease treatment is expanding, presenting promising development prospects. However, reports on the metabolic stability, plasma protein binding rate, and pharmacokinetic properties of arbutin are scarce., Aim of the Study: The aim of this study is to enrich the data of metabolic stability and pharmacokinetics of arbutin through the early pre-clinical evaluation, thereby providing some experimental basis for advancing arbutin into clinical research., Materials and Methods: We developed an efficient and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determining arbutin in plasma. We investigated the metabolic and pharmacokinetic properties of arbutin through in vitro metabolism assay, cytochrome enzymes P450 (CYP450) inhibition studies, plasma protein binding rate analysis, Caco-2 cell permeability tests, and rat pharmacokinetics to understand its in vivo performance., Results: In vitro studies show that arbutin is stable, albeit with some species differences. It exhibits low plasma protein binding (35.35 ± 11.03% ∼ 40.25 ± 2.47%), low lipophilicity, low permeability, short half-life (0.42 ± 0.30 h) and high oral bioavailability (65 ± 11.6%). Arbutin is primarily found in the liver and kidneys and is eliminated in the urine. It does not significantly inhibit CYP450 up to 10 μM, suggesting a low potential for drug interactions. Futhermore, preliminary toxicological experiments indicate arbutin's safety, supporting its potential as a therapeutic agent., Conclusion: This study provides a comprehensive analysis the drug metabolism and pharmacokinetics (DMPK) of arbutin, enriching our understanding of its metabolism stability and pharmacokinetics properties, It establishes a foundation for further structural optimization, pharmacological studies, and the clinical development of arbutin., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study investigated the long-term clinical and angiographic outcomes of encephaloduroarteriosynangiosis treatment for symptomatic intracranial atherosclerotic arterial steno-occlusive disease to further evaluate the potential therapeutic role of encephaloduroarteriosynangiosis in this population., Methods and Results: A total of 152 adult patients with symptomatic intracranial atherosclerotic arterial steno-occlusive disease who were treated with encephaloduroarteriosynangiosis and intensive medical management across 3 tertiary centers in China between January 2011 and September 2019 were retrospectively included. The primary outcomes were defined as postoperative cerebrovascular events, including ischemic and hemorrhagic stroke. The postoperative neovascularization was analyzed qualitatively and quantitatively by using angiography. Clinical, radiological, and long-term follow-up data were analyzed using Cox regression, logistic regression, and linear regression analyses. Primary outcome rates were 3.2% (5/152) within 30 days, 6.6% (10/152) within 2 years, 9.2% (14/152) within 5 years, and 11.1% (17/152) during a median 9.13 years follow-up. Initial infarction symptoms were positively associated with recurrent ischemic stroke. Additionally, posterior circulation involvement and coexisting cardiac disease indicated poorer neurological status, whereas encephaloduroarteriosynangiosis neovascularization efficacy was negatively associated with older age and vascular risk factors but positively associated with posterior circulation involvement., Conclusions: Encephaloduroarteriosynangiosis plus intensive medical management appears efficacious and safe for symptomatic intracranial atherosclerotic arterial steno-occlusive disease, with low perioperative risk and favorable long-term results. Further prospective trials are needed to verify its efficacy and determine the optimal patient selection criteria.

Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC., Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis., Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC., Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC., Competing Interests: The authors declare no conflict of interest., (Copyright 2024, Guo et al.)

Objective: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B 1 (AFB 1 ), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB 1 -induced hepatocyte injury and the mechanisms underlying those effects were investigated., Methods: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB 1 -induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB 1 was used to evaluate the effects of baicalin., Results: In vitro, baicalin significantly attenuated AFB 1 -induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB 1 -induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB 1 -treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin., Conclusions: Baicalin can alleviate AFB 1 -induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB 1 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Isolated from intertidal sediment of the Yellow Sea, China, Bremerella sp. P1 putatively represents a novel species within the genus Bremerella of the family Pirellulaceae in the phylum Planctomycetota. The complete genome of strain P1 comprises a single circular chromosome with a size of 6,955,728 bp and a GC content of 55.26%. The genome contains 5772 protein-coding genes, 80 tRNA and 6 rRNA genes. A total of 147 CAZymes and 128 sulfatases have been identified from the genome of strain P1, indicating that the strain has the capability to degrade a wide range of polysaccharides. Moreover, a gene cluster related to bacterial microcompartments (BMCs) formation containing genes encoding the shell proteins and related enzymes to metabolize fucose or rhamnose is also found in the genome of strain P1. The genome of strain P1 represents the second complete one in the genus Bremerella, expanding the understanding of the physiological and metabolic characteristics, interspecies diversity, and ecological functions of the genus., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “The complete genome sequence of the planctomycetotal bacterium Bremerella sp. P1 with abundant genes involved in polysaccharide degradation”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The intraocular injections of anti-vascular endothelial growth factor (anti-VEGF) demonstrates significant efficacy in inhibiting the formation of ocular neovascularization in neovascular glaucoma (NVG). Ahmed glaucoma valve implantation (AGVI) is extensively employed for the management of diverse glaucoma types., Objective: To further evaluate the efficacy and safety of anti-VEGF combined with AGVI in the treatment of neovascular glaucoma., Methods: A thorough search for randomized controlled trials (RCTs) was conducted across eight databases: PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. The search period was set from the inception of each database until March 2, 2024, to identify RCTs investigating the effectiveness and safety of combining AGVI with anti-VEGF therapy for NVG. We used the Cochrane Risk of Bias Assessment Tool to evaluate the quality of the literature and performed statistical analysis using Stata 15.0 software., Results: Fourteen RCTs were included in this study. Compared with AGVI alone, the combination of anti-VEGF drugs and AGVI can reduce postoperative intraocular pressure (IOP) at 1 week [WMD = -4.03, 95% CI (-5.73, -2.34), p  < 0.001], 1 month [WMD = -5.39, 95% CI (-7.05, -3.74), p  < 0.001], 3 months [WMD = -6.59, 95% CI (-7.85, -5.32), p  < 0.001], 6 months [WMD = -4.99, 95% CI (-9.56, -0.43), p  = 0.032], and more than 12 months [WMD = -3.86, 95% CI (-6.82, -0.90), p  = 0.011], with a higher Effective rate [RR = 1.27, 95% CI (1.18, 1.37), p  < 0.001], decreased incidence of postoperative hyphema [RR = 0.24, 95% CI (0.15, 0.39), p  < 0.001], reduced use of postoperative antiglaucoma medications [WMD = -0.48, 95% CI (-0.61, -0.35), p  < 0.001], and decreased aqueous humor VEGF levels [SMD = -2.84, 95% CI (-4.37, -1.31), p  < 0.001]., Conclusion: In comparison to AGVI alone, the combination of AGVI with anti-VEGF therapy has better effects in reducing IOP at various time intervals, diminishing postoperative antiglaucoma medication requirements and reducing aqueous humor VEGF levels. Furthermore, it effectively minimizes the incidence of postoperative hyphema. Nevertheless, due to the variability in the quality of the trials included, further high-quality experiments will be required in the future to substantiate this conclusion., Systematic Review Registration: PROSPERO, identifier CRD42024519862, https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42024519862., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Lu, Zeng, Liu, Qiu, Xue and He.)

Background: Whether patients can benefit from three-field lymphadenectomy (3-FL) in minimally invasive esophagectomy (MIE) remains unclear. This study retrospectively compared short-term outcomes between 3-FL and two-field lymphadenectomy (2-FL) in MIE for patients with esophageal cancer (EC) and aimed to evaluate the clinical significance of 3-FL., Methods: There were 284 patients enrolled in the study (124 patients with 3-FL and 160 patients with 2-FL). The cases were matched based on their propensity scores using a matching ratio of 1:1, the nearest neighbor matching protocol, and a caliper of 0.02. Patients were propensity-score matched for sex, cancer location, Age-adjusted Charlson Comorbidity Index (ACCI), and neoadjuvant treatment. The short-term outcomes were postoperative complications, operation characteristics, pathology results and postoperative hospital stay., Results: There were no significant differences in intraoperative hemorrhage, postoperative hospital stay, or postoperative complications between the 2-FL and 3-FL groups. The operation time of the two groups was significantly different (227.1±46.2 vs. 248.5±45.9 min, P=0.001); the operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group. The number of lymphatic nodes (LNs) obtained in the 3-FL group was significantly higher than that in the 2-FL group (31.3±12.9 vs. 54.6±18.0, P<0.001). Pathological N stage was also significantly different (P=0.002); the 3-FL group was more advanced than the 2-FL group., Conclusions: Compared to 2-FL MIE, 3-FL MIE does not increase postoperative complications, can obtain more LNs, and improves the accuracy of tumor LN staging., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2356/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Background: Renal stones ranging 20-40 mm are very common in China. Although no large-sample clinical studies have confirmed the clinical efficacy and safety of this method, there is also a lack of comparative data with traditional treatment., Aim: To investigate the clinical efficacy of flexible ureteroscopy (FURS) and percutaneous nephrolithotomy (PCNL) by postoperative stone clearance and changes in soluble vascular cell adhesion molecule 1 (sVCAM-1) and kidney injury molecule 1 (KIM-1) levels in patients with large kidney stones (> 2 cm in diameter)., Methods: This single-center observational study was performed at a Chinese hospital between January 1, 2021, and October 30, 2023. All 250 enrolled patients were diagnosed with large kidney stones (> 2 cm) and divided into a FURS group ( n = 145) and a PCNL group ( n = 105) by the surgical method. The FURS group was treated with flexible ureteroscopy and the PCNL group was treated with percutaneous nephrolithotomy. The operation time, time to palinesthesia, intraoperative blood loss, drop in hemoglobin, length of hospital stay, stone clearance rate, and complications were recorded in the two groups. Preoperative and postoperative serum sVCAM-1 levels, erythrocyte sedimentation rate (ESR), urine KIM-1 levels, preoperative and postoperative pain visual analog scale (VAS) and Wisconsin Stone Quality of Life Questionnaire (WISQOL) scores were also documented., Results: All 250 eligible patients completed the follow-up. There were no significant differences in baseline characteristics between the two groups ( P > 0.05). The operation time in the FURS group was significantly greater than that in the PCNL group. The time to ambulation, intraoperative blood loss, decrease in hemoglobin, and length of hospital stay were significantly lower in the FURS group than in the PCNL group. The FURS group also had a significantly higher stone clearance rate and a lower incidence of postoperative complications. There was no significant difference in antibiotic use between the groups. Postoperative serum sVCAM-1 levels, urine KIM-1 levels, and VAS scores were lower in the FURS group than in the PCNL group, but postoperative ESR and WISQOL scores were greater in the FURS group than in the PCNL group., Conclusion: FURS demonstrated superior clinical efficacy in treating large kidney stones (> 2 cm in diameter) compared PCNL. It not only improved the postoperative stone clearance rate and reduced complications and recovery time but also positively affected serum SCM-1, ESR, and urine KIM-1 levels, subsequent improvement of patient quality of life., Competing Interests: Conflict-of-interest statement: All researchers state that there are no conflicting interests in this investigation., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Nowadays in our society, lung cancer is exhibiting a high mortality rate and threat to human health. Conventional diagnostic techniques used in the field of lung cancer often necessitate the use of extensive instrumentation, exhibit a tendency for false positives, and are not suitable for widespread early screening purposes. Conventional approaches to treat lung cancer primarily involve surgery, chemotherapy, and radiotherapy. However, these broad-spectrum treatments suffer from drawbacks such as imprecise targeting and significant side effects, which restrict their widespread use. Metal-organic frameworks (MOFs) have attracted significant attention in the diagnosis and treatment of lung cancer owing to their tunable electronic properties and structures and potential applications. These porous nanomaterials are formed through the intricate assembly of metal centers and organic ligands, resulting in highly versatile frameworks. Compared to traditional diagnostic and therapeutic modalities, MOFs can improve the sensitivity of lung cancer biomarker detection in the diagnosis of lung cancer. In terms of treatment, they can significantly reduce side effects and improve therapeutic efficacy. Hence, this perspective provides an overview concerning the advancements made in the field of MOFs as potent biosensors for lung cancer biomarkers. It also delves into the latest research dealing with the use of MOFs as carriers for drug delivery. Additionally, it explores the applications of MOFs in various therapeutic approaches, including chemodynamic therapy, photodynamic therapy, photothermal therapy, and immunotherapy. Furthermore, this review comprehensively analyses potential applications of MOFs as biosensors in the field of lung cancer diagnosis and combines different therapeutic approaches aiming for enhanced therapeutic efficacy. It also presents a concise overview of the existing obstacles, aiming to pave the way for future advancements in lung cancer diagnosis and treatment.

Objective: The present study aimed to explore the function of human bone marrow mesenchymal stem cells (hBMMSCs)-derived exosomal long noncoding RNA histocompatibility leukocyte antigen complex P5 (HCP5) in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to improve chronic periodontitis (CP)., Methods: Exosomes were extracted from hBMMSCs. Alizarin red S staining was used to detect mineralised nodules. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure HCP5 and miR-24-3p expression. The mRNA and protein levels of alkaline phosphatase ( ALP ), osteocalcin, osterix, runt-related transcription factor 2, bone morphogenetic protein 2, osteopontin, fibronectin, collagen 1, heme oxygenase 1 ( HO1 ), P38 , and ETS transcription factor ELK1 ( ELK1) were detected using RT-qPCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the HO1 and carbon monoxide concentrations. Heme, biliverdin, and Fe 2+ levels were determined using detection kits. Micro-computed tomography, hematoxylin and eosin staining, ALP staining, tartrate-resistant acid phosphatase staining, ELISA, and RT-qPCR were conducted to evaluate the effect of HCP5 on CP mice. Dual luciferase, RNA immunoprecipitation, and RNA pulldown experiments were performed to identify the interactions among HCP5, miR-24-3p, and HO1 ., Results: The osteogenic ability of hPDLSCs significantly increased when co-cultured with hBMMSCs or hBMMSCs exosomes. Overexpression of HCP5 and HO1 in hBMMSCs exosomes promoted the osteogenic differentiation of hPDLSCs, and knockdown of HCP5 repressed the osteogenic differentiation of hPDLSCs. HCP5 knockdown enhanced the inflammatory response and repressed osteogenesis in CP mice. MiR-24-3p overexpression diminished the stimulatory effect of HCP5 on the osteogenic ability of hPDLSCs. Mechanistically, HCP5 acted as a sponge for miR-24-3p and regulated HO1 expression, and HO1 activated the P38 / ELK1 pathway., Conclusion: HBMMSCs-derived exosomal HCP5 promotes the osteogenic differentiation of hPDLSCs and alleviates CP by regulating the miR-24-3p/ HO1 / P38 / ELK1 signalling pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

A silver-catalyzed protocol for the intermolecular radical umpolung cross-coupling protocol of silyl enol ethers with activated methylene compounds is disclosed. The protocol exhibits excellent functional group tolerance, enabling the expedient preparation of a variety of tricarbonyl compounds. Preliminary mechanistic investigations suggest that the reaction proceeds through a process involving free radicals in which silver oxide has a dual role, acting as both a catalyst and a base.

Purpose: Our research aims to compare the predictive performance of decision tree algorithms (DT) and logistic regression analysis (LR) in constructing models, and develop a Post-Thrombotic Syndrome (PTS) risk stratification tool., Methods: We retrospectively collected and analyzed relevant case information of 618 patients diagnosed with DVT from January 2012 to December 2021 in three different tertiary hospitals in Jiangxi Province as the modeling group. Additionally, we used the case information of 212 patients diagnosed with DVT from January 2022 to January 2023 in two tertiary hospitals in Hubei Province and Guangdong Province as the validation group. We extracted electronic medical record information including general patient data, medical history, laboratory test indicators, and treatment data for analysis. We established DT and LR models and compared their predictive performance using receiver operating characteristic (ROC) curves and confusion matrices. Internal and external validations were conducted. Additionally, we utilized LR to generate nomogram charts, calibration curves, and decision curves analysis (DCA) to assess its predictive accuracy., Results: Both DT and LR models indicate that Year, Residence, Cancer, Varicose Vein Operation History, DM, and Chronic VTE are risk factors for PTS occurrence. In internal validation, DT outperforms LR (0.962 vs 0.925, z = 3.379, P < 0.001). However, in external validation, there is no significant difference in the area under the ROC curve between the two models (0.963 vs 0.949, z = 0.412, P = 0.680). The validation results of calibration curves and DCA demonstrate that LR exhibits good predictive accuracy and clinical effectiveness. A web-based calculator software of nomogram (https://sunxiaoxuan.shinyapps.io/dynnomapp/) was utilized to visualize the logistic regression model., Conclusions: The combination of decision tree and logistic regression models, along with the web-based calculator software of nomogram, can assist healthcare professionals in accurately assessing the risk of PTS occurrence in individual patients with lower limb DVT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Pancreatic serous cystic neoplasm (SCN) is a benign cystic neoplasm that is likely to be surgically resected due to preoperative misdiagnosis or tentative diagnosis even using endoscopic ultrasonography (EUS). We aimed to analyze EUS findings of SCN associated with misdiagnosis., Methods: Between January 2012 and September 2023, histologically confirmed pancreatic SCN were included and EUS features were reviewed., Results: Overall, 294 patients with 300 surgically resected SCNs were included. The median age of the patients was 51 years and 75.9% were females. The lesions were predominantly located in the body/neck/tail of the pancreas (63.0%). The overall preoperative diagnostic rate of SCN was 36.3%, with the most common misdiagnosis being intraductal papillary mucinous neoplasm (IPMN) (31.3%), while 16.3% remained undefined. The preoperative diagnostic rate of SCN varied across different endosonographic morphologies, with oligocystic, macrocystic, microcystic, and solid patterns yielding rates of 12.8%, 37.9%, 76.5%, and 19.2%, respectively. Notably, the presence of central scar and vascularity improved the diagnostic accuracy and correctly identified 41.4% and 52.3% of the lesions. While mucus or pancreatic duct (PD) communication significantly increased the likelihood of misdiagnosis, particularly as IPMN. Multivariate analysis revealed a morphological pattern, mucin-producing signs, wall thickening, vascularity, and PD communication were independent factors related to preoperative misdiagnosis, with an overall accuracy of 82.3%., Conclusions: Preoperative diagnosis of SCN remains challenging. The microcystic pattern emerged as a reliable feature, while mucin-producing signs, including mural nodules, mucus, and PD communication, pose diagnostic pitfalls despite the presence of typical central scar or vascularity commonly in SCN., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

This study established an ultra-performance liquid chromatography(UPLC) fingerprint of abandoned stems and leaves of Artemisia selengensis and quantitative analysis of multi-components by single marker(QAMS) for five phenolic acid components. Waters Acquity UPLC BEH C&#95;(18) chromatography column(2.1 mm×100 mm, 1.7 μm) was used. The gradient elution was carried out with the mobile phase composed of 0.1% phosphoric acid water and acetonitrile at a flow rate of 0.3 mL·min~(-1) and a column temperature at 30 ℃. The detection wavelength was 330 nm, and the injection volume was 2 μL. Similarity evaluation and cluster analysis were conducted on the fingerprint data, and 15 common components in 13 batches of abandoned stems and leaves of A. selengensis were identified. The relative correction factors of ferulic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C were calculated using chlorogenic acid as the internal reference. The QAMS for determining five components in the abandoned stems and leaves of A. selengensis was established. At the same time, the content of these five components was determined using the external standard method(ESM), and the results showed that there were no significant differences in their content determined by the QAMS and the ESM. The results indicated that the content of phenolic acid components in the abandoned stems and leaves of A. selengensis from different varieties and different origins had obvious differences. In addition, the content of phenolic acid components in the abandoned stems and leaves of lignified A. selengensis was significantly higher than that of non-lignified A. selengensis. In summary, QAMS established in this study can be quickly, accurately, and economically used to determine the content of five phenolic acid components in abandoned stems and leaves of A. selengensis, laying a foundation for the resource development and utilization of abandoned stems and leaves of A. selengensis.

This article explores the standardized management of colorectal polyps, including classification, treatment, follow-up, and preventive control. Corresponding treatment strategies, including endoscopic resection and surgical intervention, are employed for different types of polyps. Currently, there is debate over whether to choose endoscopic resection or surgical intervention for malignant polyps at pT1 stage. Drawing on the latest literature and guidelines, the article elaborates on polyp classification, treatment modalities, follow-up, and preventive measures. Standardized management of colorectal polyps is important for reducing the incidence of colorectal cancer and improving the cure rate of early-stage colorectal cancer.

Electroactive bacteria, exemplified by Shewanella oneidensis MR-1, have garnered significant attention due to their unique extracellular electron-transfer (EET) capabilities, which are crucial for energy recovery and pollutant conversion. However, the practical application of MR-1 is constrained by its EET efficiency, a key limiting factor, due to the complexity of research methodologies and the challenges associated with the practical use of gene editing tools. To address this challenge, a novel gene integration system, INTEGRATE, was developed, utilizing CRISPR-mediated transposase technologies for precise genomic insertion within the S. oneidensis MR-1 genome. This system facilitated the insertion of extensive gene segments at different sites of the Shewanella genome with an efficiency approaching 100%. The inserted cargo genes could be kept stable on the genome after continuous cultivation. The enhancement of the organism's EET efficiency was realized through two primary strategies: the integration of the phenazine-1-carboxylic acid synthesis gene cluster to augment EET efficiency and the targeted disruption of the SO3350 gene to promote anodic biofilm development. Collectively, our findings highlight the potential of utilizing the INTEGRATE system for strategic genomic alterations, presenting a synergistic approach to augment the functionality of electroactive bacteria within bioelectrochemical systems.

Objective: To investigate the morbidity of cerebrovascular disease among residents ≥30 years in Pengzhou, Sichuan Province, and analyze the effect of physical activity level on the risk of morbidity of cerebrovascular disease. Methods: From 2004 to 2008, people from Pengzhou, Sichuan Province were randomly selected. All the local people aged 30-79 were asked to receive a questionnaire survey, physical examination, and long-term follow-up to determine the morbidity of cerebrovascular disease. The physical activity level and the morbidity of cerebrovascular disease were described, and Cox proportional hazard regression models were used to evaluate the association of domain-specific physical activity with the risk of morbidity of cerebrovascular disease. Results: In 55 126 participants, there were 5 290 new cases of cerebrovascular disease, with a cumulative incidence of 9.60%. After the adjustment for multiple confounding factors, multivariate Cox proportional hazard regression analysis showed that increased levels of occupational, transportation, and total physical activity reduced the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). The highest group of occupational physical activity level had the lowest risk of cerebrovascular disease, with a hazard ratio ( HR ) value of 0.81 (95% CI : 0.75-0.88), the highest group of transportation physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.84 (95% CI : 0.78-0.91), the highest group of total physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.87 (95% CI : 0.80-0.94), compared with the lowest group of corresponding physical activity. No association was found between the household/leisure-time physical activity level and the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Conclusions: In project areas of Pengzhou, Sichuan Province, increased physical activity has been associated with reduced morbidity of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Increased levels of physical activity in adults are encouraged for health benefits.

All-inorganic perovskites show great promise as an emission layer in perovskite light-emitting diodes (PeLEDs) owing to their easy solution processing, low manufacturing cost, and excellent optoelectronic properties. However, there is still an immense performance gap from small-area devices to large-area PeLED devices. The inhomogeneity of large-area high-quality perovskite films inevitably leads to vast defects and electroluminescence performance losses. Herein, a post-hot-cast annealing deposition scheme and the introduction of the multifunctional molecule 2-amino-1,3-propanediol (APDO) were proposed to regulate the crystallization of the perovskite film. As a result, uniform APDO:CsPbBr 2.5 Cl 0.5 perovskite films with high crystallinity and lower defect density were deposited by post-hot-cast annealing. A decent maximum brightness of 2659 cd m -2 was achieved for the large-area cyan PeLEDs with an emitting area of 400 mm 2 ., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)